Hepatobiliary Pancreat Dis Int

	2024 Vol. 23 No. 2
	Published: 2024-04-15


	Pages 111-220
	REVIEW ARTICLES ORIGINAL ARTICLES/Liver NEW TECHNIQUES Special issue on LT and Alternative Treatments in HB Oncology

Special issue on LT and Alternative Treatments in HB Oncology

	111	Lerut J
		Liver transplantation and liver resection as alternative treatments for primary hepatobiliary and secondary liver tumors: Competitors or allies? ^Hot!
		Although Starzl designed in the 1960’s liver transplantation (LT) to treat unresectable primary and also secondary liver tumors, transplantation still occupies a (too) small place in the respective therapeutic algorithms [1] . Due to the lack of (any) selection criteria, the concept of transplantation became rapidly challenged because of the prohibitively high incidence of tumor recurrence [1–3] . Not surprisingly, the “oncological pendulum” reversed in the nineties and moved the indication for LT from large multifocal lesions to a more limited tumor burden. In fact the paradigm changed towards transplanting the resectable and resecting the “untransplantable” cancer [4] . More recently the pendulum is going again in the opposite direction based on major progresses made in the medico-surgical treatment of these different tumors [5–14] . Seen the great potential of LT in the treatment of liver tumors, our team introduced in 2015 in the medical literature the term “transplant oncology” in clinical practice [15] .
		Hepatobiliary Pancreat Dis Int. 2024; 23(2): 111-116 . [Abstract] ( 16 ) [HTML 1KB] [PDF 0KB] ( 48 )

	117	Yang X, Lu L, Zhu WW, Tao YF, Shen CH, Chen JH, Wang ZX, Qin LX
		Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges ^Hot!
		Hepatectomy is still the major curative treatment for patients with liver malignancies. However, it is still a big challenge to remove the tumors in the central posterior area, especially if their location involves the retrohepatic inferior vena cava and hepatic veins. Ex vivo liver resection and auto-transplantation (ELRA), a hybrid technique of the traditional liver resection and transplantation, has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation. Due to its technical difficulty, ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation. The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases, especially in the advanced alveolar echinococcosis. Recently, the application of ELRA for liver malignances has gained more attention. However, standardization of clinical practice norms and international consensus are still lacking. The prognostic impact in these oncologic pa- tients also needs further evaluation. In this review, we summarized the principles and recent progresses on ELRA.
		Hepatobiliary Pancreat Dis Int. 2024; 23(2): 117-122 . [Abstract] ( 17 ) [HTML 1KB] [PDF 0KB] ( 29 )

	123	Bhangui P
		Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective? ^Hot!
		Patients with locally advanced hepatocellular cancer (HCC) and portal vein tumor thrombosis (PVTT) have a dismal prognosis since limited treatment options are available for them. In recent years, effective sys- temic therapy, and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy, have given some hope to prolong survival in them. This review summarized re- cent evidence in literature regarding the possible role of liver resection (LR) and liver transplantation (LT) in patients with locally advanced HCC and PVTT with no extrahepatic disease. Downstaging therapies have helped make curative resection or LT a reality in selected patients. This review emphasizes on the key points to focus on when considering surgery in these patients, who are usually relegated to palliative systemic therapy alone. Meticulous patient selection based on tumor biology, documented downstaging based on imaging and decrease in tumor marker levels, and an adequate waiting period to demonstrate stable disease, may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.
		Hepatobiliary Pancreat Dis Int. 2024; 23(2): 123-128 . [Abstract] ( 14 ) [HTML 1KB] [PDF 0KB] ( 55 )

	129	Kodali S, Connor AA, Thabet S, Brombosz EW, Ghobrial RM
		Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions ^Hot!
		Intrahepatic cholangiocarcinoma (iCCA) is a rare biliary tract cancer with high mortality rate. Complete resection of the iCCA lesion is the first choice of treatment, with good prognosis after margin-negative resection. Unfortunately, only 12%-40% of patients are eligible for resection at presentation due to cirrhosis, portal hypertension, or large tumor size. Liver transplantation (LT) offers margin-negative iCCA extirpation for patients with unresectable tumors. Initially, iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes. Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA. Another selection criterion is the tumor response to neoadjuvant therapy. Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor re- sponse to neoadjuvant therapy. Another index that helps predict the treatment outcome is the biomarker. Improved survival outcomes have also opened the door for living donor LT for iCCA. Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection. The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.
		Hepatobiliary Pancreat Dis Int. 2024; 23(2): 129-138 . [Abstract] ( 19 ) [HTML 1KB] [PDF 0KB] ( 70 )

	139	Andraus W, Tustumi F, Santana AC, Pinheiro RSN, Waisberg DR, Lopes LD, Arantes RM, Santos VR, de Martino RB, D’Albuquerque LAC
		Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review
		Background: Perihilar cholangiocarcinoma (phCCC) is a dismal malignancy. There is no consensus regarding the best treatment for patients with unresectable phCCC. The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice. Data sources: The search was conducted in PubMed, Embase, Cochrane, and LILACS. The related references were searched manually. Inclusion criteria were: reports in English or Portuguese literature that a) patients with confirmed diagnosis of phCCC; b) patients treated with a curative intent; c) patients with the outcomes of liver resection and liver transplantation. Case reports, reviews, letters, editorials, conference abstracts and papers with full-text unavailability were excluded from the analysis. Results: Most of the current literature is based on observational retrospective studies with low grades of evidence. Liver resection has better long-term outcomes than systemic chemotherapy or palliation therapy and liver transplantation is a good alternative for selected patients with unresectable phCCC. All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahepatic diseases. As a general rule, patients presenting with a tumor having a longitudinal size > 3 cm or extending below the cystic duct, lymph node disease, confirmed extrahepatic dissemination; intraoperatively diagnosed metastatic disease; a history of other malignancies within the last five years, and did not complete chemoradiation regimen and were medically unfit should not be considered for transplantation. Some of these criteria should be individually assessed. Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers, and any decision-making must be based on a multidisciplinary evaluation. Conclusions: phCCC is a complex condition with high morbidity. Surgical therapies, including hepatectomy and liver transplantation, are the best option for better long-term disease-free survival.
		Hepatobiliary Pancreat Dis Int. 2024; 23(2): 139-145 . [Abstract] ( 11 ) [HTML 1KB] [PDF 0KB] ( 42 )

	146	Muller PC, Pfister M, Eshmuminov D, Lehmann K
		Liver transplantation as an alternative for the treatment of neuroendocrine liver metastasis: Appraisal of the current evidence
		Background: Liver transplantation (LT) for neuroendocrine liver metastases (NELM) is still in debate. Studies comparing LT with liver resection (LR) for NELM are scarce, as patient selection is heterogeneous and experience is limited. The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM. Data sources: A scoping literature search on LT and LR for NELM was performed with PubMed, including English articles up to March 2023. Results: International guidelines recommend LR for NELM in resectable, well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies. Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival. In highly selected patients (based on the Milan criteria) with unresectable NELM, oncologic results of LT are promising. Prognostic factors include tumor biology (G1/G2) and burden, waiting time for LT, patient age and extrahepatic spread. Based on low-level evidence, LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR. The benefits of LT were lost in patients beyond the Milan NELM-criteria. Conclusions: With adherence to strict selection criteria especially tumor biology, LT for NELM is becoming a valuable option providing oncologic benefits compared to LR. Recent evidence suggests even stricter selection criteria with regard to tumor biology.
		Hepatobiliary Pancreat Dis Int. 2024; 23(2): 146-153 . [Abstract] ( 12 ) [HTML 1KB] [PDF 0KB] ( 90 )

	154	Rawashdeh B, Bell R, Hakeem A, Prasad R
		Liver transplantation as an alternative for the treatment of non-resectable liver colorectal cancer: Advancing the therapeutic algorithm
		Colorectal cancer is a leading cause of cancer-related mortality, with nearly half of the affected patients developing liver metastases. For three decades, liver resection (LR) has been the primary curative strategy, yet its applicability is limited to about 20% of cases. Liver transplantation (LT) for unresectable metastases was attempted unsuccessfully in the 1990s, with high rates of perioperative death and recurrence. There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques. A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60% chance of survival after five years. Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria, especially in the Norvegian SECA trials. This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases. The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced, highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.
		Hepatobiliary Pancreat Dis Int. 2024; 23(2): 154-159 . [Abstract] ( 8 ) [HTML 1KB] [PDF 0KB] ( 86 )

REVIEW ARTICLES

	160	Qian ZB, Li JF, Xiong WY, Mao XR
		Ferritinophagy: A new idea for liver diseases regulated by ferroptosis
		Background: The discovery of regulatory cell death has led to a breakthrough in the therapeutic field. Various forms of cell death, such as necrosis, apoptosis, pyroptosis, autophagy, and ferroptosis, play an important role in the development of liver diseases. In general, more than one form of cell death pathways is responsible for the disease state. Therefore, it is particularly important to study the regulation and interaction of various cell death forms in liver diseases. Data sources: We performed a PubMed search up to November 2022 with the following keywords: ferritinophagy, ferroptosis, and liver disease. We also used terms such as signal path, inducer, and inhibitor to supplement the query results. Results: This review summarized the basic characteristics of ferritinophagy and ferroptosis and the regulation of ferroptosis by ferritinophagy and reviewed the key targets and treatment strategies of ferroptosis in different liver diseases. Conclusions: Ferritinophagy is a potential therapeutic target in ferroptosis-related liver diseases.
		Hepatobiliary Pancreat Dis Int. 2024; 23(2): 160-170 . [Abstract] ( 10 ) [HTML 1KB] [PDF 0KB] ( 93 )

	171	Xiang Z, He XL, Zhu CW, Yang JJ, Huang L, Jiang C, Wu J; Chinese Consortium for the Study of Hepatitis E (CCSHE)
		Animal models of hepatitis E infection: Advances and challenges
		Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis worldwide. Although most of HEV infections are asymptomatic, some patients will develop the symptoms, especially pregnant women, the elderly, and patients with preexisting liver diseases, who often experience anorexia, nausea, vomiting, malaise, abdominal pain, and jaundice. HEV infection may become chronic in immunosuppressed individuals. In addition, HEV infection can also cause several extrahepatic manifestations. HEV exists in a wide range of hosts in nature and can be transmitted across species. Hence, animals susceptible to HEV can be used as models. The establishment of animal models is of great significance for studying HEV transmission, clinical symptoms, extrahepatic manifestations, and therapeutic strategies, which will help us understand the pathogenesis, prevention, and treatment of hepatitis E. This review summarized the animal models of HEV, including pigs, monkeys, rabbits, mice, rats, and other animals. For each animal species, we provided a concise summary of the HEV genotypes that they can be infected with, the crossspecies transmission pathways, as well as their role in studying extrahepatic manifestations, prevention, and treatment of HEV infection. The advantages and disadvantages of these animal models were also emphasized. This review offers new perspectives to enhance the current understanding of the research landscape surrounding HEV animal models.
		Hepatobiliary Pancreat Dis Int. 2024; 23(2): 171-180 . [Abstract] ( 11 ) [HTML 1KB] [PDF 0KB] ( 63 )

ORIGINAL ARTICLES/Liver

	181	Tomita M, Ogura T, Hakoda A, Ueno S, Okuda A, Nishioka N, Yamamoto Y, Nishikawa H
		Propensity score matching analysis for clinical impact of braided-type versus laser-cut-type covered self-expandable metal stents for endoscopic ultrasound-guided hepaticogastrostomy
		Background: To prevent stent migration during endoscopic ultrasound-guided hepaticogastrostomy (EUS- HGS), intra-scope channel release technique is important, but is unfamiliar to non-expert hands. The self expandable metal stent (SEMS) is an additional factor to prevent stent migration. However, no comparative studies of laser-cut-type and braided-type during EUS-HGS have been reported. The aim of this study was to compare the distance between the intrahepatic bile duct and stomach wall after EUS-HGS among laser-cut-type and braided-type SEMS. Methods: To evaluate stent anchoring function, we measured the distance between the hepatic parenchyma and stomach wall before EUS-HGS, one day after EUS-HGS, and 7 days after EUS-HGS. Also, propensity score matching was performed to create a propensity score for using laser-cut-type group and braided-type group. Results: A total of 142 patients were enrolled in this study. Among them, 24 patients underwent EUS-HGS using a laser-cut-type SEMS, and 118 patients underwent EUS-HGS using a braided-type SEMS. EUS-HGS using the laser-cut-type SEMS was mainly performed by non-expert endoscopists ( n = 21); EUS-HGS using braided-type SEMS was mainly performed by expert endoscopists ( n = 98). The distance after 1 day was significantly shorter in the laser-cut-type group than that in the braided-type group [2.00 (1.70- 3.75) vs. 6.90 (3.72-11.70) mm, P < 0.001]. In addition, this distance remained significantly shorter in the laser-cut-type group after 7 days. Although these results were similar after propensity score matching analysis, the distance between hepatic parenchyma and stomach after 7 days was increased by 4 mm compared with the distance after 1 day in the braided-type group. On the other hand, in the laser-cut-type group, the distance after 1 day and 7 days was almost the same. Conclusions: EUS-HGS using a laser-cut-type SEMS may be safe to prevent stent migration, even in non-expert hands.
		Hepatobiliary Pancreat Dis Int. 2024; 23(2): 181-185 . [Abstract] ( 12 ) [HTML 1KB] [PDF 0KB] ( 33 )

	186	Feng MX, Zou H, Lu YQ
		Severe liver injury and clinical characteristics of occupational exposure to 2-amino-5-chloro-N,3-dimethylbenzamide: A case series
		Background: The 2-amino-5-chloro-N,3-dimethylbenzamide is a key intermediate in the synthesis of pesticides and pharmaceuticals. However, no literature currently exists on 2-amino-5-chloro-N,3- dimethylbenzamide poisoning in humans. This study aimed to reveal the health hazard of this chemical for humans and summarize the clinical characteristics of patients with occupational 2-amino-5-chloro- N,3-dimethylbenzamide poisoning. Methods: This observational study included four patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning from June 2022 to July 2022. The entire course of the incidents was described in detail. Blood 2-amino-5-chloro-N,3-dimethylbenzamide concentrations were detected by a mass spectrometer. Hema- toxylin and eosin staining was performed to assess liver injury, and immunofluorescence was used to evaluate hepatic mitophagy. Results: The 2-amino-5-chloro-N,3-dimethylbenzamide powder (99% purity) entered the human body mainly via the skin and respiratory tract due to poor personal protective measures. The typical course of 2-amino-5-chloro-N,3-dimethylbenzamide poisoning was divided into latency, rash, fever, organic damage, and recovery phases in accordance with the clinical evolution. Rash and fever may be the important premonitory symptoms for further organ injuries. The chemical was detected in the blood of all patients and caused multiple organ injuries, predominantly liver injury, including kidney, myocardium, and micro- circulation. Three patients recovered smoothly after comprehensive treatments, including artificial liver therapy, continuous renal replacement therapy, glucocorticoids, and other symptomatic and supportive treatments. One patient survived by liver transplantation. The postoperative pathological findings of the removed liver showed acute liver failure, and immunofluorescence staining confirmed the abundance of mitophagy in residual hepatocytes. Conclusions: This study is the first to elaborate the clinical characteristics of patients with 2-amino- 5-chloro-N,3-dimethylbenzamide poisoning. The chemical enters the body through the respiratory tract and skin during industrial production. The 2-amino-5-chloro-N,3-dimethylbenzamide poisoning causes multiple-organ dysfunction with a predominance of liver injury. Liver transplantation may be an effective option for patients with severe liver failure. The mechanisms of liver injury induced by 2-amino-5-chloro- N,3-dimethylbenzamide might involve abnormal mitochondrial function and mitophagy.
		Hepatobiliary Pancreat Dis Int. 2024; 23(2): 186-194 . [Abstract] ( 11 ) [HTML 1KB] [PDF 0KB] ( 63 )

	195	Zhang Y, Wang ZZ, Han AQ, Yang MY, Zhu LX, Pan FM, Wang Y
		TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways
		Background: As reported, γ-tubulin (TuBG1) is related to the occurrence and development of various types of malignant tumors. However, its role in hepatocellular cancer (HCC) is not clear. The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients. Methods: The correlation between TuBG1 and clinical parameters and survival in HCC patients was explored by bioinformatics analysis. Immunohistochemistry was used for the verification. The molecular function of TuBG1 was measured using colony formation, scratch assay, trans-well assay and flow cytometry. Gene set enrichment analysis (GSEA) was used to pick up the enriched pathways, followed by investigating the target pathways using Western blotting. The tumor-immune system interactions and drug bank database (TISIDB) was used to evaluate TuBG1 and immunity. Based on the TuBG1-related immune genes, a prognostic model was constructed and was further validated internally and externally. Results: The bioinformatic analysis found high expressed TuBG1 in HCC tissue, which was confirmed using immunohistochemistry and Western blotting. After silencing the TuBG1 in HCC cell lines, more G1 arrested cells were found, cell proliferation and invasion were inhibited, and apoptosis was promoted. Furthermore, the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3 (ATR), phospho-P38 mitogen-activated protein kinase (P-P38MAPK), phospho-P53 (P-P53), B-cell lymphoma-2 associated X protein (Bax), cleaved caspase 3 and P21; decreased the expressions of B-cell lymphoma-2 (Bcl-2), cyclin D1, cyclin E2, cyclin-dependent kinase 2 (CDK2) and CDK4. The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre- lated with the overall survival. The constructed immune prognosis model could effectively evaluate the prognosis. Conclusions: The increased expression of TuBG1 in HCC is associated with poor prognosis, which might be involved in the occurrence and development of HCC.
		Hepatobiliary Pancreat Dis Int. 2024; 23(2): 195-209 . [Abstract] ( 10 ) [HTML 1KB] [PDF 0KB] ( 35 )

NEW TECHNIQUES

	210	Guo Q, Wang ML, Zhong K, Li JL, Jiang TM, Wen H, Aji T, Shao YM
		*Portal vein embolization combined with ex vivo* liver resection and autotransplantation: A novel treatment strategy for end-stage and metastatic hepatic alveolar echinococcosis**
		Alveolar echinococcosis (AE) is a lethal parasitic disease caused by Echinococcus multilocularis larvae, and more than 90% of primary AE lesions occur in the liver. Most of the affected individuals remain asymptomatic and the disease is often diagnosed at an advanced stage. The infection may spread to organs adjacent to the liver or distant locations, eventually causing end-stage multiple organ AE. Brain metastasis of AE is the most fatal with an incidence rate of 0.2% [1] . End-stage AE has a mortality rate of 90% if left untreated [2] . When important blood vessels such as the confluence of three hepatic veins and retrohepatic inferior vena cava are invaded, in vivo R0 resection and reconstruction of these vessels are extremely burdensome [3] . In recent years, ex vivo liver resection and autotransplantation (ELRA) has been used as one of the radical treatment modalities for patients with end-stage hepatic AE [4] . However, in most patients, large or multiple lesions invade important blood vessels, resulting in insufficient future liver remnant volume (FLRV). Several techniques that promote the proliferation of hepatic lobes including portal vein embolization (PVE) and two-stage hepatectomy (TSH) may induce compensatory hypertrophy and hyperplasia of the healthy-side hepatic lobes [5–7] . When FLRV is greater than 30% of total liver volume (TLV), ELRA then may be performed to guarantee operation safety and avoid the occurrence of postoperative liver failure. Here, we reported a rare case of hepatic AE with insufficient FLRV combined with brain metastasis, which was successfully treated through PVE and ELRA.
		Hepatobiliary Pancreat Dis Int. 2024; 23(2): 210-216 . [Abstract] ( 11 ) [HTML 1KB] [PDF 0KB] ( 50 )

	217	Yu SF, Zhang WC, Yu J
		Laparoscopic anatomical liver resection of segment 7 using a sandwich approach to the right hepatic vein (with video)
		Full laparoscopic liver resection has been performed widely since it was introduced in the early 1990s. It has been expanded from initial for partial resection of the anterolateral segments to non-restriction of area of the liver [1–3] . Anatomical liver resection is considered to have potential superiority than non-anatomic resection in terms of tumor prognosis, thus it is more often recommended in the treatment of hepatocellular carcinoma [ 4 , 5 ]. Recently, laparoscopic segmental liver resection according to the Couinaud classification has been widely performed due to its advantages in minimal invasiveness and tumor prognosis.
		Hepatobiliary Pancreat Dis Int. 2024; 23(2): 217-220 . [Abstract] ( 12 ) [HTML 1KB] [PDF 0KB] ( 72 )

Forgot your password?

Enter your e-mail address to receive an e-mail with your account information.

Submission Guidance

Top cited articles

- Most Cited Hepatobiliary & Pancreatic Diseases International Articles

- Most Downloaded Hepatobiliary & Pancreatic Diseases International Articles

more>>

Top downloaded articles

more>>

Services

Web feed

hbpdint@126.com

hbpdje@zju.edu.cn

Copyright © Official Publication of First Affiliated Hospital
Official Publication of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
浙ICP备05050873号-1